Severe Combined Immune Deficiency (SCID) includes a spectrum of lethal genetic disorders resulting in profound deficiencies of T and B cell development and/or function, which render affected patients incapable of mounting protective immune responses against exogenous pathogens. Historically, children afflicted with SCID rarely survived the first year of life, succumbing to severe infections. The first cure of SCID was achieved in 1968 by transplantation of bone marrow (hematopoietic cell transplant - HCT) from an HLA compatible normal sibling, resulting in reconstitution of both T and B cell immunity. Since that time, more than 700 SCID patients in North America have been treated with HCT from matched siblings, haplo-identical parents, or unrelated adult donors or umbilical cord blood. While outcomes are generally good, not all patients survive and multiple patient-, donor- and transplant procedural differences may underlie the prognosis in each case. We have constructed a multi-institutional consortium to study this large cohort of patients, with the goal of identifying prognostic factors and defining optimal treatment approaches.
In Specific Aim 1, we will perform a retrospective analysis of patients with the different forms of SCID who have received HCT at the participating institutions. We will analyze the impact that patient-, donor-, and transplantrelated factors have on long-term outcome. This study will also provide the first multicenter analysis of the effects of SCID genotype on the outcome of transplant.
In Specific Aim 2, we will perform a cross-sectional analysis of long-term survivors after HCT for SCID, to characterize current level of T, B and NK cell chimerism and function, and clinical status in terms of health, growth and both physical and neurocognitive development. We will then analyze these results in relation to information gathered in the retrospective study to determine whether and to what degree SCID genotype, type of transplant applied or other clinical variables contribute to the patient's long-term outcome. These studies will produce important information on the outcomes of HCT for SCID and guide future clinical trials.

Public Health Relevance

Primary immune deficiencies (PIDs) are rare, life-threatening inherited defects in the immune system. This retrospective and cross-sectional study of severe combined immunodeficiency disease (SCID) will help accomplish the Primary Immune Deficiency Treatment Consortium (PIDTC)'s overall objective of elucidating the prognostic factors for patients with SCID undergoing HCT to lead to the development of future therapeutic clinical trials.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
San Francisco
United States
Zip Code
Punwani, Divya; Kawahara, Misako; Yu, Jason et al. (2017) Lentivirus Mediated Correction of Artemis-Deficient Severe Combined Immunodeficiency. Hum Gene Ther 28:112-124
Heimall, Jennifer; Logan, Brent R; Cowan, Morton J et al. (2017) Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. Blood 130:2718-2727
Heimall, Jennifer; Puck, Jennifer; Buckley, Rebecca et al. (2017) Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immunodeficiency Patients: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium Biol Blood Marrow Transplant 23:379-387
Wahlstrom, Justin; Patel, Kiran; Eckhert, Erik et al. (2017) Transplacental maternal engraftment and posttransplantation graft-versus-host disease in children with severe combined immunodeficiency. J Allergy Clin Immunol 139:628-633.e10
Dorsey, Morna J; Dvorak, Christopher C; Cowan, Morton J et al. (2017) Treatment of infants identified as having severe combined immunodeficiency by means of newborn screening. J Allergy Clin Immunol 139:733-742
Dietz, Andrew C; Duncan, Christine N; Alter, Blanche P et al. (2017) The Second Pediatric Blood and Marrow Transplant Consortium International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Defining the Unique Late Effects of Children Undergoing Hematopoietic Cell Transplantation f Biol Blood Marrow Transplant 23:24-29
Kumánovics, Attila; Lee, Yu Nee; Close, Devin W et al. (2017) Estimated disease incidence of RAG1/2 mutations: A case report and querying the Exome Aggregation Consortium. J Allergy Clin Immunol 139:690-692.e3
Hoenig, Manfred; Lagresle-Peyrou, Chantal; Pannicke, Ulrich et al. (2017) Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome. Blood 129:2928-2938
Lee, Yu Nee; Frugoni, Francesco; Dobbs, Kerry et al. (2016) Characterization of T and B cell repertoire diversity in patients with RAG deficiency. Sci Immunol 1:
Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D et al. (2016) Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol 138:375-85

Showing the most recent 10 out of 74 publications